Ghazale Kazemi - Department of Chemistry, Faculty of Science, Malayer University, Malayer, Iran.
Yasin Gholiee - Department of Chemistry, Faculty of Science, Malayer University, Malayer, Iran.

Since discovery of cisplatin, many efforts have been devoted to understand the mechanisms associated with its antitumor activity, which are nowadays quite well established [1]. The primary target of cisplatin is genomic DNA, and more especially the N7 position of guanine bases. Although there is no doubt that a Pt−N7 bond forms during initial attack, the exact structure of the monofunctional adduct is not well known [2]. A better understanding at the molecular level of the interactions between the Pt and DNAbuilding blocks can be helpful in establishing a new strategy to design cisplatin analogues. In this work we report a theoretical study on the interaction of bispidine analogue of cisplatin [(C7H14N2)PtCl2] (1; see Figure 1) with guanine, at BP86/def2- TZVP level of theory. Since the guanine has three possible binding sites with the transition metal, all isomers and conformers of 1-guanine complexes were optimized. The calculated relative free energies and interaction energies between 1 and guanine showed that the preferred binding site of guanine to complex 1 (similar to cisplatin) is N7. To investigate the nature of interaction between 1 and guanine, the EDA-NOCV and NBO analyses were also performed on 1-guanine complex. The results of energy decomposition analysis, at BP86-D3/TZ2P level of theory, for all complexes show that the electrostatic nature of interaction between 1 and guanine is more than the covalent (~60% versus ~35%) and contribution of dispersion forces is ~5%.